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Woodward M, Previs MJ, Mader TJ, et al. Modifications of myofilament protein phosphorylation and function in response to cardiac arrest induced in a swine model. Front Physiol. 2015;6:199doi: 10.3389/fphys.2015.00199.
Woodward, M., Previs, M. J., Mader, T. J., & Debold, E. P. (2015). Modifications of myofilament protein phosphorylation and function in response to cardiac arrest induced in a swine model. Frontiers in physiology, 6199. https://doi.org/10.3389/fphys.2015.00199
Woodward, Mike, et al. "Modifications of myofilament protein phosphorylation and function in response to cardiac arrest induced in a swine model." Frontiers in physiology vol. 6 (2015): 199. doi: https://doi.org/10.3389/fphys.2015.00199
Woodward M, Previs MJ, Mader TJ, Debold EP. Modifications of myofilament protein phosphorylation and function in response to cardiac arrest induced in a swine model. Front Physiol. 2015 Jul 16;6:199. doi: 10.3389/fphys.2015.00199. eCollection 2015. PMID: 26236240; PMCID: PMC4503891.
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Front Physiol. 2015 Jul 16;6:199. doi: 10.3389/fphys.2015.00199. eCollection 2015.

Modifications of myofilament protein phosphorylation and function in response to cardiac arrest induced in a swine model.

Frontiers in physiology

Mike Woodward, Michael J Previs, Timothy J Mader, Edward P Debold

Affiliations

  1. Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, MA, USA.
  2. Department of Molecular Physiology and Biophysics, University of Vermont Burlington, VT, USA.
  3. Department of Emergency Medicine, Baystate Medical Center/Tufts University School of Medicine Springfield, MA, USA.
  4. Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, MA, USA ; Muscle Biophysics Lab, Department of Kinesiology, University of Massachusetts Amherst, MA, USA.

PMID: 26236240 PMCID: PMC4503891 DOI: 10.3389/fphys.2015.00199

Abstract

Cardiac arrest is a prevalent condition with a poor prognosis, attributable in part to persistent myocardial dysfunction following resuscitation. The molecular basis of this dysfunction remains unclear. We induced cardiac arrest in a porcine model of acute sudden death and assessed the impact of ischemia and reperfusion on the molecular function of isolated cardiac contractile proteins. Cardiac arrest was electrically induced, left untreated for 12 min, and followed by a resuscitation protocol. With successful resuscitations, the heart was reperfused for 2 h (IR2) and the muscle harvested. In failed resuscitations, tissue samples were taken following the failed efforts (IDNR). Actin filament velocity, using myosin isolated from IR2 or IDNR cardiac tissue, was nearly identical to myosin from the control tissue in a motility assay. However, both maximal velocity (25% faster than control) and calcium sensitivity (pCa50 6.57 ± 0.04 IDNR vs. 6.34 ± 0.07 control) were significantly (p < 0.05) enhanced using native thin filaments (actin+troponin+tropomyosin) from IDNR samples, suggesting that the enhanced velocity is mediated through an alteration in muscle regulatory proteins (troponin+tropomyosin). Mass spectrometry analysis showed that only samples from the IR2 had an increase in total phosphorylation levels of troponin (Tn) and tropomyosin (Tm), but both IR2 and IDNR samples demonstrated a significant shift from mono-phosphorylated to bis-phosphorylated forms of the inhibitory subunit of Tn (TnI) compared to control. This suggests that the shift to bis-phosphorylation of TnI is associated with the enhanced function in IDNR, but this effect may be attenuated when phosphorylation of Tm is increased in tandem, as observed for IR2. There are likely many other molecular changes induced following cardiac arrest, but to our knowledge, these data provide the first evidence that this form cardiac arrest can alter the in vitro function of the cardiac contractile proteins.

Keywords: cardiac arrest; motility; myosin; phosphorylation; resuscitation; troponin

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